The long-term goal of the proposed research is to define relationships that may exist between specific genetic markers, the inflammatory response to injury, and post-injury organ dysfunction. To accomplish this goal we shall collect and store data from patients with acute thermal injury, the most quantitative inflammatory stimulus experienced by humans. In the initial studies we shall look for associations between (a) two allelic polymorphisms in or near the TNF-alpha locus on chromosome 6, (b) blood cytokine markers of pro- and anti-inflammatory responses, and (c) specific measures of organ dysfunction. This approach should make it possible to define, for the first time, clinically relevant interactions between specific genetic polymorphisms, the production of TNF-alpha and other mediators, and inflammation-induced organ dysfunction. The CNA and data to be stored will also make it possible to assess other inflammation-related polymorphisms that are identified in the future. In addition to providing novel insights into pathogenesis, the proposed research should uncover genetic and/or acute inflammatory response parameters that correlate with subsequent organ dysfunction-that identify patients at "high risk"- and could therefore significantly improve the management of patients with thermal injury.